COX-1

SAN FRANCISCO, Nov. 10, 2022 (GLOBE NEWSWIRE) -- Nurix Therapeutics, Inc. (Nasdaq: NRIX), a clinical-stage biopharmaceutical company developing targeted protein modulation drugs designed to treat patients with hematologic malignancies and solid tumors, presented initial biomarker data demonstrating successful target engagement of CBL-B in its ongoing Phase 1 clinical trial with oral dosing of NX-1607. These data are being presented at the 37th Annual Meeting of the Society for Immunotherapy of Cancer (SITC), which is being held November 8 – 12th in Boston. “We are particularly encouraged by these initial biomarker data from the Phase 1 trial of NX-1607 measured in patients with advanced malignancies, which demonstrate remarkable concordance with levels observed in preclinical studies that are associated with potent anti-tumor activity,” said Robert J. Brown, M.D., Nurix’s executive vice president of clinical development. “The proximal biomarker of CBL-B inhibition in activated T cells can be measured in whole blood and demonstrate dose-dependence in our clinical studies enabling us to assess target engagement in the clinic and guide our selection of an appropriate dose for further expansion of the trial.” Arthur T. Sands, M.D., Ph.D., president and chief executive officer of Nurix, added, "Our multiple presentations at SITC illustrate the progress we have made in the development of our first-in-class CBL-B inhibitors. Of particular importance is the work we have done to identify, validate, and clinically implement assays of a key proximal biomarker of CBL-B inhibition which has enabled the first-in-human testing of NX-1607 and its novel mechanism of action. We look forward to providing additional clinical updates for NX-1607 in 2023.” Summary of data presented at the SITC Annual Meeting: NX-1607 Program Title: Initial clinical characterization of novel proximal biomarkers for NX-1607, a first-in-class oral CBL-B inhibitor, in patients with advanced malignancies Nurix has identified and characterized novel proximal biomarkers including phosphorylated hematopoietic lineage cell-specific protein 1 (pHS1) whose levels increase when CBL-B is inhibited and can be measured in ex vivo stimulated whole blood in animals and humans indicating the ability of these cells to become activated in the presence of an antigen signal such as those found in the tumor microenvironment. pHS1 is an important downstream signal of T cell activation. Preliminary pharmacokinetics and pharmacodynamic measurement of pHS1 were used to characterize the activity of NX-1607 in a first-in-human clinical trial (NCT05107674). These data demonstrate dose-responsive target engagement as measured by increases in biomarker levels in stimulated human whole blood with NX-1607 treatment reaching levels associated with anti-tumor activity in animal models at dose level 1 (5 mg) and increasing at higher doses. Preliminary PK data suggest NX-1607 has dose-proportional exposures and a mean half-life of 6 to 8 hours at doses ranging from 5 mg to 50 mg. Title: NX-1607, a small molecule inhibitor of the CBL-B E3 ubiquitin ligase, promotes T and NK cell activation and enhances NK-mediated ADCC in a mouse lymphoma tumor model These studies demonstrate that in addition to enhancing T-cell activation, NX-1607 renders T cells resistant to Treg and TGF-β-mediated suppression. In addition, the data demonstrate that NX-1607 treatment augments NK cell activity both in vitro, in an antibody-dependent cellular cytotoxicity (ADCC) assay using human NK cells, and in vivo, in a xenograft mouse tumor model. In a murine xenograft model of non-Hodgkin’s lymphoma (NHL), the combination of NX-1607 and rituximab (anti-CD20 Mab) significantly enhanced tumor growth inhibition and tumor rejections when compared to single agents' activity. Importantly, the survival benefit provided by the combination of NX-1607 plus rituximab was abrogated by depletion of NK cells. About NX-1607 NX-1607 is an orally bioavailable inhibitor of Casitas B-lineage lymphoma proto-oncogene B (CBL-B) for immuno-oncology indications, including a range of solid tumor types. NX-1607 acts on T cells, NK cells, and dendritic cells to enhance anti-tumor immunity, and has demonstrated single-agent anti-tumor activity in multiple tumor models. Nurix is evaluating NX-1607 in an ongoing, Phase 1 dose escalation and expansion trial in adults with a variety of oncology indications at multiple clinical sites. Additional information on the clinical trial can be accessed at www.clinicaltrials.gov (NCT05107674). About Nurix Therapeutics, Inc. Nurix Therapeutics is a clinical stage biopharmaceutical company focused on the discovery, development and commercialization of small molecule and cell therapies based on the modulation of cellular protein levels as a novel treatment approach for cancer and other challenging diseases. Leveraging extensive expertise in E3 ligases together with its proprietary DNA-encoded libraries, Nurix has built DELigase, an integrated discovery platform to identify and advance novel drug candidates targeting E3 ligases, a broad class of enzymes that can modulate proteins within the cell. Nurix’s drug discovery approach is to either harness or inhibit the natural function of E3 ligases within the ubiquitin proteasome system to selectively decrease or increase cellular protein levels. Nurix’s wholly owned pipeline includes targeted protein degraders of Bruton’s tyrosine kinase, a B-cell signaling protein, and inhibitors of Casitas B-lineage lymphoma proto-oncogene B, an E3 ligase that regulates T cell activation. Nurix is headquartered in San Francisco, California. For additional information visit http://www.nurixtx.com.

Biomarker results are a positive demonstration of target engagement for this first-in-class CBL-B inhibitor Biomarker levels achieved with NX-1607 treatment correspond to levels associated with potent anti-tumor activity in disease models SAN FRANCISCO, Nov. 10, 2022 (GLOBE NEWSWIRE) -- Nurix Therapeutics Inc. (Nasdaq: NRIX), a clinical-stage biopharmaceutical company developing targeted protein modulation drugs designed to treat patients with hematologic malignancies and solid tumors, presented initial biomarker data demonstrating successful target engagement of CBL-B in its ongoing Phase 1 clinical trial with oral dosing of NX-1607. These data are being presented at the 37th Annual Meeting of the Society for Immunotherapy of Cancer (SITC), which is being held November 8 – 12th in Boston. “We are particularly encouraged by these initial biomarker data from the Phase 1 trial of NX-1607 measured in patients with advanced malignancies, which demonstrate remarkable concordance with levels observed in preclinical studies that are associated with potent anti-tumor activity,” said Robert J. Brown, M.D., Nurix’s executive vice president of clinical development. “The proximal biomarker of CBL-B inhibition in activated T cells can be measured in whole blood and demonstrate dose-dependence in our clinical studies enabling us to assess target engagement in the clinic and guide our selection of an appropriate dose for further expansion of the trial.” Arthur T. Sands, M.D., Ph.D., president and chief executive officer of Nurix, added, "Our multiple presentations at SITC illustrate the progress we have made in the development of our first-in-class CBL-B inhibitors. Of particular importance is the work we have done to identify, validate, and clinically implement assays of a key proximal biomarker of CBL-B inhibition which has enabled the first-in-human testing of NX-1607 and its novel mechanism of action. We look forward to providing additional clinical updates for NX-1607 in 2023.” Summary of data presented at the SITC Annual Meeting: NX-1607 Program Title: Initial clinical characterization of novel proximal biomarkers for NX-1607, a first-in-class oral CBL-B inhibitor, in patients with advanced malignancies Nurix has identified and characterized novel proximal biomarkers including phosphorylated hematopoietic lineage cell-specific protein 1 (pHS1) whose levels increase when CBL-B is inhibited and can be measured in ex vivo stimulated whole blood in animals and humans indicating the ability of these cells to become activated in the presence of an antigen signal such as those found in the tumor microenvironment. pHS1 is an important downstream signal of T cell activation. Preliminary pharmacokinetics and pharmacodynamic measurement of pHS1 were used to characterize the activity of NX-1607 in a first-in-human clinical trial (NCT05107674). These data demonstrate dose-responsive target engagement as measured by increases in biomarker levels in stimulated human whole blood with NX-1607 treatment reaching levels associated with anti-tumor activity in animal models at dose level 1 (5 mg) and increasing at higher doses. Preliminary PK data suggest NX-1607 has dose-proportional exposures and a mean half-life of 6 to 8 hours at doses ranging from 5 mg to 50 mg. Title: NX-1607, a small molecule inhibitor of the CBL-B E3 ubiquitin ligase, promotes T and NK cell activation and enhances NK-mediated ADCC in a mouse lymphoma tumor model These studies demonstrate that in addition to enhancing T-cell activation, NX-1607 renders T cells resistant to Treg and TGF-β-mediated suppression. In addition, the data demonstrate that NX-1607 treatment augments NK cell activity both in vitro, in an antibody-dependent cellular cytotoxicity (ADCC) assay using human NK cells, and in vivo, in a xenograft mouse tumor model. In a murine xenograft model of non-Hodgkin’s lymphoma (NHL), the combination of NX-1607 and rituximab (anti-CD20 Mab) significantly enhanced tumor growth inhibition and tumor rejections when compared to single agents' activity. Importantly, the survival benefit provided by the combination of NX-1607 plus rituximab was abrogated by depletion of NK cells. About NX-1607 NX-1607 is an orally bioavailable inhibitor of Casitas B-lineage lymphoma proto-oncogene B (CBL-B) for immuno-oncology indications, including a range of solid tumor types. NX-1607 acts on T cells, NK cells, and dendritic cells to enhance anti-tumor immunity, and has demonstrated single-agent anti-tumor activity in multiple tumor models. Nurix is evaluating NX-1607 in an ongoing, Phase 1 dose escalation and expansion trial in adults with a variety of oncology indications at multiple clinical sites. Additional information on the clinical trial can be accessed at (NCT05107674). About Nurix Therapeutics, Inc. Nurix Therapeutics is a clinical stage biopharmaceutical company focused on the discovery, development and commercialization of small molecule and cell therapies based on the modulation of cellular protein levels as a novel treatment approach for cancer and other challenging diseases. Leveraging extensive expertise in E3 ligases together with its proprietary DNA-encoded libraries, Nurix has built DELigase, an integrated discovery platform to identify and advance novel drug candidates targeting E3 ligases, a broad class of enzymes that can modulate proteins within the cell. Nurix’s drug discovery approach is to either harness or inhibit the natural function of E3 ligases within the ubiquitin proteasome system to selectively decrease or increase cellular protein levels. Nurix’s wholly owned pipeline includes targeted protein degraders of Bruton’s tyrosine kinase, a B-cell signaling protein, and inhibitors of Casitas B-lineage lymphoma proto-oncogene B, an E3 ligase that regulates T cell activation. Nurix is headquartered in San Francisco, California. For additional information visit . Forward Looking Statement This press release contains statements that relate to future events and expectations and as such constitute forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. When or if used in this press release, the words “anticipate,” “believe,” “could,” “estimate,” “expect,” “intend,” “may,” “outlook,” “plan,” “predict,” “should,” “will,” and similar expressions and their variants, as they relate to Nurix, may identify forward-looking statements. All statements that reflect Nurix’s expectations, assumptions or projections about the future, other than statements of historical fact, are forward-looking statements, including, without limitation, statements regarding the therapeutic potential and other advantages of NX-1607 and Nurix’s other drug candidates; the planned timing and conduct of the clinical trials for NX-1607 and Nurix’s other drug candidates; the planned timing for the provision of updates and findings from Nurix’s clinical trials; the extent animal model data predicts human efficacy; and the extent to which Nurix’s drug candidates and scientific approach may potentially address a broad range of diseases. Forward-looking statements reflect Nurix’s current beliefs, expectations, and assumptions. Although Nurix believes the expectations and assumptions reflected in such forward-looking statements are reasonable, Nurix can give no assurance that they will prove to be correct. Forward-looking statements are not guarantees of future performance and are subject to risks, uncertainties and changes in circumstances that are difficult to predict, which could cause Nurix’s actual activities and results to differ materially from those expressed in any forward-looking statement. Such risks and uncertainties include, but are not limited to: (i) whether Nurix will be able to successfully conduct Phase 1 clinical trials for NX-1607 and its other drug candidates and receive results on its expected timelines, or, at all; (ii) whether Nurix will be able to successfully complete clinical development for NX-1607 and its other drug candidates; (iii) the risk that clinical trial data are subject to differing interpretations and assessments by regulatory authorities; (iv) whether regulatory authorities will be satisfied with the results from Nurix’s clinical studies; (v) whether Nurix will be able to obtain regulatory approval of and ultimately commercialize its drug candidates; (vi) whether Nurix will be able to fund development activities and achieve development goals; (vii) the impact of the COVID-19 pandemic on Nurix’s clinical trials and operations; and (viii) other risks and uncertainties described under the heading “Risk Factors” in Nurix’s Quarterly Report on Form 10-Q for the fiscal quarter ended August 31, 2022, and other SEC filings. Accordingly, readers are cautioned not to place undue reliance on these forward-looking statements. The statements in this press release speak only as of the date of this press release, even if subsequently made available by Nurix on its website or otherwise. Nurix disclaims any intention or obligation to update publicly any forward-looking statements, whether in response to new information, future events, or otherwise, except as required by applicable law. Contacts: Silinda Neou Nurix Therapeutics ir@nurixtx.com Elizabeth Wolffe, Ph.D. Wheelhouse Life Science Advisors lwolffe@wheelhouselsa.com Media Brett Whelan LifeSci Communications bwhelan@lifescicomms.com

Dec. 1, 2021 12:05 UTC New Potential Treatment Targets Millions of Fibromyalgia Patients Worldwide First Ever FDA “Fast Track” Designation for Fibromyalgia Development Candidate Phase 2b Clinical Trial Builds on Positive Phase 2a Data ATLANTA--(BUSINESS WIRE)-- Virios Therapeutics, Inc. (Nasdaq: VIRI), a development-stage biotechnology company focused on advancing novel antiviral therapies to treat debilitating chronic diseases, including fibromyalgia, announced today that more than 50% of the patients planned for the Phase 2b FORTRESS (Fibromyalgia Outcome Research Trial Evaluating Synergistic Suppression of HSV-1) study have been randomized. The FORTRESS study is a randomized, double-blind evaluation of IMC-1 in patients with fibromyalgia (“FM”). Worldwide, FM affects 3-6% of the population and is characterized by widespread chronic pain and multiple symptoms often including severe fatigue, sleep disruption and cognitive dysfunction. Based on Virios market analysis, we estimate that only 15% of FM treatment prescribers report satisfaction with existing treatment options. The FORTRESS study builds on the statistically significant results from the Company’s previously completed Phase 2a FM clinical study. The 143-patient Phase 2a trial demonstrated that IMC-1 met its primary endpoint of pain reduction and was statistically better tolerated than placebo. “We are pleased that enrollment in our FORTRESS trial is progressing rapidly, with careful patient selection and the support of more than 40 U.S. clinical sites,” said R. Michael Gendreau, M.D., Ph.D., Chief Medical Officer of Virios Therapeutics. “We are very grateful for the physicians at these sites and their patients for their commitment and willingness to participate in this critical FM trial, especially during a pandemic. Reaching this enrollment milestone on a timely basis indicates that we are currently on track to report top line results in Q3 of 2022.” Greg Duncan, Chairman and CEO of Virios, stated, “Fibromyalgia is a chronic disease that affects 10 million patients in the U.S. As many as 40% of FM patients are being treated with opioids, according to market surveys. This is particularly troubling given FM patients treated with opioids have been shown to experience worse outcomes among multiple assessment domains. Consistent with our mission, Virios Therapeutics is developing the non-opioid IMC-1 with the end goal of advancing care for hundreds of millions of patients globally in need of new FM treatment options.” Virios’ lead antiviral development candidate, orally administered IMC-1, is a novel, proprietary, fixed dose, antiviral therapy combining famciclovir and celecoxib. This dual mechanism antiviral therapy is designed to synergistically suppress Herpes Simplex Virus-1 (“HSV-1”) activation and replication. The uniqueness of this approach has garnered IMC-1 “fast track” designation by the U.S. Food and Drug Administration (FDA), the first of its kind for a new FM development candidate. It is the Company’s hypothesis that HSV-1 related immune responses can serve as a catalyst for symptoms commonly associated with FM, irritable bowel syndrome (“IBS”) and related disorders. This hypothesis is supported by both clinical and mechanistic data, the latter of which has suggested that HSV-1 is actively replicating in the tissue of patients diagnosed with FM and chronic GI disorders, such as IBS. For more information, please visit . About IMC-1 IMC-1 is a novel, proprietary, fixed dose combination of famciclovir and celecoxib. This dual mechanism antiviral therapy is designed to synergistically suppress HSV-1 activation and replication. IMC-1 combines two specific mechanisms of action purposely selected to inhibit HSV-1 activation and replication, thereby keeping HSV-1 in a latent (dormant) state or “down-regulating” HSV-1 from a lytic (active) state back to latency. The famciclovir component of IMC-1 inhibits viral DNA polymerase necessary for replication. The celecoxib component of IMC-1 inhibits both cyclooxegenase-2 (“COX-2”) and COX-1 enzymes, used by HSV-1 to accelerate its own replication. Virios Therapeutics holds a U.S. “Composition of Matter” Synergistic Patent (US 10,251,853) for the synergistic combination for total daily dose of famciclovir and celecoxib. About Virios Therapeutics Virios Therapeutics (Nasdaq: VIRI) is a development-stage biotechnology company focused on advancing novel antiviral therapies to treat debilitating chronic diseases, such as fibromyalgia (“FM”). Immune responses related to the activation of tissue resident Herpes Simplex Virus-1 (“HSV-1”) have been postulated as a potential root cause triggering and/or sustaining chronic illnesses such as FM, irritable bowel disease (“IBS”), chronic fatigue syndrome and other functional somatic syndromes, all of which are characterized by waxing and waning symptoms with no obvious etiology. Our lead development candidate (“IMC-1”) is a novel, proprietary, fixed dose combination of famciclovir and celecoxib designed to synergistically suppress HSV-1 replication, with the end goal of reducing virally promoted disease symptoms. Evidence of IMC-1’s efficacy on a broad spectrum of FM outcome measures was previously demonstrated in a Phase 2a clinical trial. These trial results are suggestive that IMC-1 may represent a new and novel treatment for fibromyalgia. IMC-1 has been granted fast track designation by the FDA and is currently being tested in a multi-center, randomized, double-blind, placebo-controlled Phase 2b trial (“FORTRESS”) designed to set the stage for registrational studies. The Company is led by an executive team highly experienced in the successful development and commercialization of novel therapies. For more information, please visit . Forward-Looking Statements Statements in this press release contain “forward-looking statements”, within the meaning of the U.S. Private Securities Litigation Reform Act of 1995, that are subject to substantial risks and uncertainties. All statements, other than statements of historical fact, contained in this press release are forward-looking statements. Forward-looking statements contained in this press release may be identified by the use of words such as “anticipate,” “believe,” “contemplate,” “could,” “estimate,” “expect,” “intend,” “seek,” “may,” “might,” “plan,” “potential,” “predict,” “project,” “suggest,” “target,” “aim,” “should,” "will,” “would,” or the negative of these words or other similar expressions, although not all forward-looking statements contain these words. Forward-looking statements are based on Virios Therapeutics’ current expectations and are subject to inherent uncertainties, risks and assumptions that are difficult to predict, including risks related to the completion and timing of the FORTRESS trial. Further, certain forward-looking statements are based on assumptions as to future events that may not prove to be accurate. These and other risks and uncertainties are described more fully in the section titled “Risk Factors” in the Annual Report on Form 10-K for the year ended December 31, 2020 filed with the Securities and Exchange Commission. Forward-looking statements contained in this announcement are made as of this date, and Virios Therapeutics, Inc. (VIRI) undertakes no duty to update such information except as required under applicable law.